Huntington’s breakthrough may stop disease

[Ron]

I thought some here might find this article interesting. I posted a few interesting excerpts from the article.

http://www.bbc.com/news/health-42308341


An experimental drug, injected into spinal fluid, safely lowered levels of toxic proteins in the brain.
The research team, at University College London, say there is now hope the deadly disease can be stopped.
Experts say it could be the biggest breakthrough in neurodegenerative diseases for 50 years.




The unstoppable death of brain cells in Huntington's leaves patients in permanent decline, affecting their movement, behaviour, memory and ability to think clearly.





Huntington's is caused by an error in a section of DNA called the huntingtin gene.
Normally this contains the instructions for making a protein, called huntingtin, which is vital for brain development.
But a genetic error corrupts the protein and turns it into a killer of brain cells.
The treatment is designed to silence the gene.





But the principle that a gene, any gene affecting disease progression and susceptibility, can be safely modified in this way in humans is very exciting and builds momentum and confidence in pursuing these avenues for potential treatments."

 

[Piper]

I saw that article. I wonder how far away it is from being accessible to all?

At what point would it halt disease progression? Could it be used on those already in mid to late stage disease?

Huntingtons is a horrible disease.

 

[Alvin]

That is insanely good news
I hope they don't price it out of reach or destroy the life savings of sufferers.

 

[arewenearlythereyet]

I saw this on the news last night too. They certainly got top billing on the 6 O clock news.

I guess if this is relevant for PWME (or a sub set of them) they would need to find a genetic link for this to be relevant (if I have understood the science right).

It is fantastic news for Huntingdons though and possibly many other genetic conditions that affect the brain.

 

[Esther12]

Fingers crossed it all work out for them. That would be amazing.

 

[Piper]

Huntingtons lives in my close circle of people. I don't have any words to describe how cruel it is.

It's been interesting as it's gotten more exposure in the entertainment media here in Australia lately. Twice it's been mentioned accurately in Australian made new drama/sit coms over the past few months.

 

[Forbin]

Another article from The Washington Post:

'Phenomenal' trial results may lead to a treatment for Huntington's disease, experts say

The good news for Huntington's patients is the hope that the drug might even reverse the progression of the disease.

“What's really interesting in animal studies, if you stop the production of the mutant protein, not only does progression stop, but the brain starts to heal itself,” said Christopher Ross, director of the Huntington's Disease Center at Johns Hopkins Medicine, who was not involved in the research. “Which means there might be improvement.”

https://www.washingtonpost.com/news...s-disease-experts-say/?utm_term=.10b70d9fd5f8

 

[Little Bluestem]

Huntington's is caused by an error in a section of DNA called the huntingtin gene.
Normally this contains the instructions for making a protein, called huntingtin, which is vital for brain development.
But a genetic error corrupts the protein and turns it into a killer of brain cells.
The treatment is designed to silence the gene.

If the silenced, corrupt gene is still not producing the huntingtin protein which is vital for brain development, isn't the person still going to have problems?

 

[Forbin]

If the silenced, corrupt gene is still not producing the huntingtin protein which is vital for brain development, isn't the person still going to have problems?

I wondered about this. I also wonder how often the drug has to be administered. I think it has to be injected into the spine and there might be issues with doing that repeatedly. Still, these concerns no doubt pale compared to the consequences of the untreated disease.

 

[Valentijn]

If the silenced, corrupt gene is still not producing the huntingtin protein which is vital for brain development, isn't the person still going to have problems?

I can't find a copy of the paper yet, or even an abstract, but the lead author's recent work says this about the general subject:

Attempting to target the full-length mutant HTT mRNA, whilst leaving the mRNA of the wild-type allele unaffected, has proven to be very difficult in cells derived from HD patients (although newer strategies are being developed to try and do just that—see later). An alternative approach is to non-specifically lower both mutant and wild-type HTT to a degree which improves pathology whilst maintaining safety and tolerability in the face of wild-type HTT loss. A 40–60% reduction in both endogenous and mutant HTT extends the lifespan and prevents motor deficits, without causing toxicity in both fragment [26] and full-length [17] mouse models of HD.

Huntingtin's is autosomal dominant, meaning patients usually just have one bad copy of the gene. Ideally, you'd want to turn off the bad copy and leave the good copy running normally, but the technology doesn't exist yet. So the solution for now is dial down the production of both the good and bad copies, so the bad ones don't cause as much damage, while there's still enough good copies produced to carry out the necessary functions of the gene.

This makes sense, since genes don't need to be at 100% of their possible functionality to function acceptably, or even optimally. From what I saw when reading research into methylation and similar mutations, there's typically little or no health problem until functionality gets to under 25-30%. So cutting the protein production in half probably is pretty safe, and would be in line with the article reporting no side effects from this treatment.

But that means that this technique isn't a cure. It's a temporary reprieve, and the toxic protein continues to be produced and cause damage. It's just slowing it down quite a bit, so probably extending lifetime and functionality somewhat.

 

[TrixieStix]

https://ipscell.com/2017/12/hope-hype-on-unpublished-huntingtons-disease-trial-splashy-news/

"The splashy news a couple days ago that there may have been a “major breakthrough” on Huntington’s Disease caught my eye. I was hoping that there was concrete reason for optimism such as a new paper and no hype here.

Unfortunately, it feels to me like this Huntington’s Disease story was premature and hyped in the media in some cases. It’s not fair to patients to oversell scientific developments and especially to make bold statements before papers are published. Again, Huntington’s is a terrible disease. The patient advocacy community has been hard at work to advance new transformative therapies so they deserve balanced coverage."